RESUMEN
Elephantopus tomentosus (ET) Linn. was reported to be an anti-tumor plant. However, the chemical composition of ET and its anti-tumor compounds and potential mechanisms still unclear. In this paper, UPLC-Q-TOF-MS/MS was firstly used to identified the ingredients in ET and UPLC was used to determine the main compounds of ET. Network pharmacology was applied to predict the potential mechanisms of anti-liver cancer. Anti-tumor nuclear activate compounds and targets of ET were obtained and the anti-liver cancer effect was validated on HepG2. Finally, Molecule docking, RT-qPCR, and western blotting were used for verification of the relationship between nuclear activate compounds and nuclear targets and the potential anti-cancer mechanisms. The result showed that 42 compounds were identified in ET, which consisted of sesquiterpene lactones, flavonoids, and phenylpropanoid compounds. Scabertopin (ST), chlorogenic acid, Isochlorogenic acid B, Isochlorogenic acid A and Isochlorogenic acid C were identified as main compounds and were determined as 0.426%, 0.457%, 0.159%, 0.701%, and 0.103% respectively. 24 compounds showed high pharmacokinetics and good drug-likeness. 520 overlapping targets of the ET compounds and liver cancer were collected. The targets were used for KEGG and GO analysis. GO enrichment analysis suggested that the targets of 24 active compound closed related to promote apoptosis, inhibit proliferation, and regulate oxidative levels. KEGG enrichment analysis suggested that pathway in cancer was enriched most and p38 MAPK/p53 signaling pathway, which closely related to promoting apoptosis and inhibiting proliferation. Compounds-targets analysis based on the parameter of Betweenness, Closeness, Information, Eigenvector, Degree, and component content indicated that ST was the nucleus anti-tumor active compound of ET. HepG2 was first used to validated the anti-tumor effect of ST and the result showed that ST significantly inhibited HepG2 proliferation with a low IC50 less than 5 µM. Nucleus active compound targets, including TP53, CASP3, BCL2, EGFR, TNF-a, IL-1ß, and IL-6 were enriched based on degree value of PPI analysis. Molecule docking suggested that ST showed a good combination to TGFBR1 with the combination energy less than - 5 kcal/mol. RT-qPCR result also suggested that ST significantly medicated the mRNA expression level of TP53, CASP3, BCL2, EGFR, TNF-a, IL-1ß, and IL-6. Protein expression of p-p38/p38 and p-p53/p53 notable increased by ST treatment. In conclude, combining with UPLC-Q-TOF-MS/MS qualitative analysis, UPLC quantitative analysis, network pharmacology analysis, molecule docking, and in vitro experiments on HepG2, we suggest that ST is an anti-tumor ingredient of ET, which may target to TGFBR1 and promote apoptosis and inhibited proliferation of HepG2 by activating p38 MAPK/p53 signaling pathway. ST can be regarded as a quality marker of ET.
Asunto(s)
Neoplasias Hepáticas , Simulación del Acoplamiento Molecular , Humanos , Células Hep G2 , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Asteraceae/química , Simulación por Computador , Espectrometría de Masas en Tándem , Proliferación Celular/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Apoptosis/efectos de los fármacosRESUMEN
The development of products with skin-protective effects has been driven by the increasing incidence of skin diseases that are exacerbated by increasing pollution, urbanization, poor living, working, fatigue, dietary habits, and general treatment. The ability of antioxidants to protect the skin from oxidative stress and its effects makes them one of the most important ingredients in today's cosmetics. This article aims first to characterize the plant extracts obtained from Acmella oleracea (A. oleracea) and then to evaluate the preliminary criteria for a new marketed product: the stability, antioxidant activity, and in vitro behavior of certain serums based on A. oleracea plant extract and hyaluronic acid. The extracts were obtained by liquid-solid extraction methods (maceration (M), ultrasound-assisted extraction (UEA), and a combined method between these two (UEA + M) using an aqueous solution of ethyl alcohol as the extraction solvent. The determination of the amounts of compounds with antioxidant activity highlighted the fact that the extract obtained from the whole plant of A. oleracea using maceration in conditions of S/L = 1:30, 20 days, and an extraction solvent percentage of 50% led to obtaining the highest amount of polyphenols (30.42 µg GAE/g), while using the combined UAE + M method under conditions of S/L = 1:30, 6 min + 20 days, and 50% extraction solvent led to obtaining the highest amount of flavonoids (32.88 mg QE/g). The tests performed on dermato-cosmetic serums based on the plant extract and multimolecular hyaluronic acid (HA) (1 HA with HMW-1.0 mDa-1.6 mDa; HA with LMW-10 kDa-200 kDa; and HA OLIGO, MW < 10 kDa) led to the conclusion that they exhibit structural stability, good shear behavior revealing a satisfactory texture, and high physical stability during storage. These results encourage the transition to in-depth testing, both microbiological and dermatological, as a final step in the consideration of a new commercial product.
Asunto(s)
Antioxidantes , Estrés Oxidativo , Extractos Vegetales , Extractos Vegetales/química , Extractos Vegetales/farmacología , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/química , Humanos , Cosméticos/química , Piel/metabolismo , Piel/efectos de los fármacos , Piel/química , Ácido Hialurónico/química , Asteraceae/químicaRESUMEN
Twenty-nine sesquiterpenoids, including pseudoguaiane-type (1-11), eudesmane-type (12-23), and carabrane-type (24-29), have been identified from the plant Carpesium abrotanoides. Of them, compounds 1-4, 12-15, and 24-27, namely carpabrotins A-L, are twelve previously undescribed ones. Compound 3 possessed a pseudoguaiane backbone with a rearrangement modification at C-11, C-12 and C-13, while compound 4 suffered a carbon bond break between the C-4 and C-5 to form a rare 4,5-seco-pseudoguaiane lactone. Compounds 1-3, 5, 13-16 and 25-27 exhibited anti-inflammatory activity by inhibiting NO production in LPS-induced RAW264.7 macrophages with IC50 values less than 40 µM, while compounds 1, 2, 5, 13, 14, 16, and 25-27 showed significant inhibitory activity comparable to that of dexamethasone. The anti-atopic dermatitis (AD) effects of compounds 5 and 16 were tested according to 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in KM mice, and the results revealed that the major products 5 and 16 improved the histological features of AD-like skin lesions and mast cell infiltration in mice. This study suggested that sesquiterpenoids in C. abrotanoides should play a key role in its anti-inflammatory use.
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Asteraceae , Óxido Nítrico , Sesquiterpenos , Animales , Ratones , Sesquiterpenos/farmacología , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Asteraceae/química , Células RAW 264.7 , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Óxido Nítrico/metabolismo , Estructura Molecular , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Macrófagos/efectos de los fármacos , MasculinoRESUMEN
Ainsliaea fragrans Champ, a strong heat-clearing and detoxifying traditional Chinese medicine, has been effectively used for treating chronic cervicitis, endometritis, pelvic inflammatory diseases, and other conditions caused by damp heat. It shows a good effect in the treatment of cervicitis and has broad clinical application prospects. Nevertheless, there is no comprehensive study on its in vivo and in vitro chemical analysis. UHPLC-QTOF-MS/MS combined with the non-targeted characteristic filter analysis were used to conjecture and characterize the chemical components and in vivo metabolites of rats following oral administration of Ainsliaea fragrans Champ. In this study, A total of 85 compounds were identified in Ainsliaea fragrans Champ, including 29 flavonoids, 14 sesquiterpenoids, 25 chlorogenic acids, and 17 other compounds. In the plasma of rats after administration of Ainsliaea fragrans Champ, 160 compounds were deduced (19 prototype compounds and 141 metabolites). The 141 metabolites consist of 50 flavonoids, 80 phenolic acids and 11 Chlorogenic acids. The related metabolic pathways mainly involved demethylation, reduction, sulfonation, decarboxylation, hydroxylation, methylation, and glucuronide conjunction. In summary, the chemical components and metabolites of Ainsliaea fragrans Champ were comprehensively identified by using a rapid and accurate analysis method, which laid a foundation for dissecting its bioactive substances. In addition, it provides a scientific basis for the in-depth study of the material basis of Ainsliaea fragrans Champ efficacy and theoretical support for illustrating the mechanism of medical action and its clinical application.
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Medicamentos Herbarios Chinos , Flavonoides , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem , Animales , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en Tándem/métodos , Ratas , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/metabolismo , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacocinética , Administración Oral , Flavonoides/sangre , Flavonoides/química , Femenino , Ácido Clorogénico/sangre , Ácido Clorogénico/química , Ácido Clorogénico/administración & dosificación , Ácido Clorogénico/metabolismo , Asteraceae/química , Hidroxibenzoatos/sangre , Hidroxibenzoatos/análisis , Hidroxibenzoatos/metabolismoRESUMEN
Environmental pollution, being a major concern worldwide, needs a unique and ecofriendly solution. To answer this, researchers are aiming in utilizing plant extracts for the synthesis of nanoparticles. These NPs synthesized using plant extracts provide a potential, environmentally benign technique for biological and photocatalytic applications. Especially, plant leaf extracts have been safe, inexpensive, and eco-friendly materials for the production of nanoparticles in a greener way. In this work, zinc ferrite nanoparticles (ZnFe2O4 NPs) were prepared using Nyctanthes arbor-tristis leaf extract by hydrothermal method, and its biological and photocatalytic properties were assessed. The synthesized ZnFe2O4 NPs were characterized using powder X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier-transform infrared spectroscopy (FT-IR). X-ray diffraction confirmed the arrangement of the fcc crystal structure of the nanoparticles and that some organic substances were encapsulated within the zinc ferrite. According to the SEM analysis, the resulting nanoparticles got agglomerated and spherical in shape. The ZnFe2O4 nanoparticles are in their pure form, and all of their elemental compositions were shown by the energy-dispersive X-ray analysis (EDAX) spectrum. The FTIR results revealed that the produced nanoparticles contained distinctive functional groups. Fluorescence spectroscopy was used to examine the binding affinities between bovine serum albumin (BSA) and ZnFe2O4 nanoparticles in terms of protein binding, stability, and conformation. The interaction between BSA and ZnFe2O4 NPs was examined using steady-state and time-resolved fluorescence measurements, and it was evident that static quenching occurred. The ability of ZnFe2O4 nanoparticles to kill Culex quinquefasciatus (C. quinquefasciatus) larvae was evaluated. The synthesized NPs demonstrated a noteworthy toxic effect against the fourth instar larvae of C. quinquefasciatus with LC50 values of 43.529 µg/mL and LC90 values of 276.867 µg/mL. This study revealed the toxicity of green synthesized ZnFe2O4 NPs on mosquito larvae, proving that these NPs are good and effective larvicides. Furthermore, the ZnFe2O4 NPs were utilized for dye degradation of methylene blue under visible light treatment and achieved 99.5% degradation.
Asunto(s)
Compuestos Férricos , Zinc , Compuestos Férricos/química , Zinc/química , Animales , Nanopartículas/química , Tecnología Química Verde , Asteraceae/química , Larva/efectos de los fármacos , Catálisis , Extractos Vegetales/químicaRESUMEN
The present study reports the green synthesis of pectin-fabricated silver nanocomposites (Pectin-AgNPs) using Carpesium nepalense leaves extract, evaluating their bactericidal kinetics, in vivo hepatoprotective, and cytotoxic potentials along with possible mechanisms. GC/MS and LC/MS analyses revealed novel phytochemicals in the plant extract. The Pectin-AgNPs were characterized using UV/Vis, AFM, SEM, TEM, DLS, FTIR, and EDX techniques, showing a spherical morphology with a uniform size range of 50-110 nm. Significant antibacterial activity (P < 0.005) was found against four bacterial strains with ZIs of 4.1 ± 0.15 to 27.2 ± 3.84 mm. AFM studies revealed significant bacterial cell membrane damage post-treatment. At 0.05 mg/kg, the nanocomposites showed significant (P < 0.005) hepatoprotective activity in biochemical and histopathology analyses compared to the CCl4 control group. Pectin-AgNPs significantly reduced (P < 0.005) LDH, AST, ALT, ALP, and DB levels. qPCR analysis showed ameliorative effects on PPARs and Nrf2 gene expression, restoring gene alterations caused by CCl4 intoxication. In vivo acute toxicity studies confirmed low toxicity of Pectin-AgNPs in major organs. Pectin-AgNPs exhibited cytotoxic activity against HeLa cell lines at higher doses with an LC50 of 223.7 µg/mL. These findings demonstrate the potential of Pectin-AgNPs as promising antibacterial, hepatoprotective, and cytotoxic agents.
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Antibacterianos , Tecnología Química Verde , Nanocompuestos , Pectinas , Plata , Nanocompuestos/química , Plata/química , Plata/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Pectinas/química , Pectinas/farmacología , Humanos , Animales , Asteraceae/química , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Cinética , Nanopartículas del Metal/química , Masculino , Células HeLa , Ratas , Hojas de la Planta/química , Sustancias Protectoras/farmacología , Sustancias Protectoras/química , Sustancias Protectoras/síntesis química , Pruebas de Sensibilidad Microbiana , Ratones , Tetracloruro de CarbonoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Blumea balsamifera (L.) DC. (BB), the source of Blumea balsamifera oil (BBO), is an aromatic medicinal plant, renowned for its pharmacological properties and its traditional use in Southeast Asian countries such as China, Thailand, Vietnam, Malaysia, and the Philippines for centuries. Traditionally, BB has been used as a raw herbal medicine for treating various skin conditions like eczema, dermatitis, athlete's foot, and wound healing for skin injuries. AIM OF THE STUDY: This research aimed to explore the inhibitory effects of BBO on skin aging using two models: in vitro analysis with human dermal fibroblasts (HDF) under UVB-induced stress, and in vivo studies on UVA-induced dorsal skin aging in mice. The study sought to uncover the mechanisms behind BBO's anti-aging effects, specifically, its impact on cellular and tissue responses to UV-induced skin aging. MATERIALS AND METHODS: We applied doses of 10-20 µL/mL of BBO to HDF cells that had been exposed to UVB radiation to simulate skin aging. We measured cell viability, and levels of reactive oxygen species (ROS), SA-ß-gal, pro-inflammatory cytokines, and matrix metalloproteinases (MMPs). In addition, we investigated the involvement of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathways in mediating the anti-aging effects of BBO. Histopathological and biochemical analyses were conducted in a mouse model to examine the effects of BBO on UV-induced photoaging. RESULTS: UV exposure accelerated aging, and caused cellular damage and inflammatory responses through ROS-mediated pathways. In HDF cells, BBO treatment countered the UVB-induced senescence, and the recovery of cell viability was correlated to notable reductions in SA-ß-gal, ROS, pro-inflammatory cytokines, and MMPs. Mechanistically, the anti-aging effect of BBO was associated with the downregulation of the JNK/NF-κB signaling pathways. In the in vivo mouse model, BBO exhibited protective capabilities against UV-induced photoaging, which were manifested by the enhanced antioxidant enzyme activities and tissue remodeling. CONCLUSIONS: BBO effectively protects fibroblasts from UV-induced photoaging through the JNK/NF-κB pathway. Recovery from photoaging involves an increase in dermal fibroblasts, alleviation of inflammation, accelerated synthesis of antioxidant enzymes, and slowed degradation of ECM proteins. Overall, BBO enhances the skin's defensive capabilities against oxidative stress, underscoring its potential as a therapeutic agent for oxidative stress-related skin aging.
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Asteraceae , Fibroblastos , Envejecimiento de la Piel , Rayos Ultravioleta , Animales , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Humanos , Fibroblastos/efectos de los fármacos , Fibroblastos/efectos de la radiación , Ratones , Asteraceae/química , Aceites de Plantas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Supervivencia Celular/efectos de los fármacos , Piel/efectos de los fármacos , Piel/efectos de la radiación , Piel/patología , Piel/metabolismo , Masculino , FN-kappa B/metabolismo , FemeninoRESUMEN
Eight previously undescribed sesquiterpene lactones (1-8), together with six known ones (9-14) were isolated from the aerial parts of Tithonia diversifolia (Hemsl.) A. Gray. The absolute configurations of these compounds were elucidated using HRMS, NMR spectroscopy, optical rotation measurements, X-ray crystallography, and ECD. Among them, sesquiterpene lactones 2-4 share a unique carbon skeleton with a rare C-3/C-4 ring-opened structure. Compounds 1 and 8 showed moderate inhibitory effects toward CT26 murine colon carcinoma cells by promoting lipid ROS production, highlighting their potential as ferroptosis inducers.
Asunto(s)
Antineoplásicos Fitogénicos , Asteraceae , Ferroptosis , Lactonas , Sesquiterpenos , Sesquiterpenos/química , Sesquiterpenos/farmacología , Sesquiterpenos/aislamiento & purificación , Lactonas/química , Lactonas/farmacología , Lactonas/aislamiento & purificación , Ferroptosis/efectos de los fármacos , Animales , Ratones , Asteraceae/química , Estructura Molecular , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Ensayos de Selección de Medicamentos Antitumorales , Relación Estructura-Actividad , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Humanos , Proliferación Celular/efectos de los fármacos , Componentes Aéreos de las Plantas/química , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Eight undescribed guaianolide sesquiterpene lactones cicholosumins A-H and twelve known ones were isolated from the aerial parts of Cichorium glandulosum Boiss et Huet. Their structures were established by 1D and 2D NMR spectroscopic data, electronic circular dichroism, quantum chemical calculations and single crystal X-ray diffraction analysis. Compounds 9α-hydroxy-3-deoxyzaluzanin C, epi-8α-angeloyloxycichoralexin, 8-O-methylsenecioylaustricin and lactucin showed strong anti-neuroinflammation activity with IC50 values of 1.69 ± 0.11, 1.08 ± 0.23, 1.67 ± 0.28 and 1.82 ± 0.27 µM, respectively. The mechanism research indicated that epi-8α-angeloyloxycichoralexin inhibited neuroinflammation through the NF-κB and MAPK pathways.
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Lactonas , Lactonas/farmacología , Lactonas/química , Lactonas/aislamiento & purificación , Estructura Molecular , Sesquiterpenos de Guayano/química , Sesquiterpenos de Guayano/farmacología , Sesquiterpenos de Guayano/aislamiento & purificación , Asteraceae/química , Animales , Sesquiterpenos/farmacología , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Conformación Molecular , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Componentes Aéreos de las Plantas/química , Ratones , Enfermedades Neuroinflamatorias/tratamiento farmacológicoRESUMEN
Carabranolides present characteristic NMR resonances for the cyclopropane moiety, which distinctly differ from those of other compounds and were used for an NMR-guided isolation in this study. As a result, 11 undescribed carabranolides (1-11), along with five known ones (12-16), were isolated from the fruits of Carpesium abrotanoides L. Compounds 1-11 are new esters of carabrol at C-4 with different carboxylic acids. Their structures were elucidated by HRESIMS and NMR spectroscopic data analysis. The biological evaluation showed that compounds 2-4, 15, and 16 exhibited significant inhibitory activity against LPS-induced NO release with an IC50 value of 5.6-9.1 µM and dose-dependently decreased iNOS protein expression in RAW264.7 cells.
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Antiinflamatorios , Asteraceae , Frutas , Óxido Nítrico , Animales , Ratones , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Asteraceae/química , Frutas/química , Lipopolisacáridos/farmacología , Espectroscopía de Resonancia Magnética , Estructura Molecular , Óxido Nítrico/biosíntesis , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Células RAW 264.7 , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacologíaRESUMEN
Thechemical composition, antioxidant and antimicrobial activities of the essential oil from aerial parts (leaves and flowers) of Chuquiraga arcuataHarling grown in the Ecuadorian Andes were studied. One hundred and twenty-six compounds were identified in the essential oil. Monoterpene hydrocarbons (45.8%) and oxygenated monoterpenes (44.1%) had the major percentages. The most abundant compounds were camphor (21.6%), myrcene (19.5%), and 1,8-cineole (13.4%). Antioxidant activity was examined using DPPH, ABTS,and FRAP assays. The essential oil had a moderate scavenging effect and reduction of ferric ion capacity through FRAP assay. Antimicrobial activity of the essential oil was observed against four pathogenic bacteria and a fungus. The essential oil exhibited activity against all microorganism strains under test, particularly against Candida albicansand Staphylococcus aureuswith MICs of 2.43-12.10 µg/mL.
Se estudió la composición química, actividades antioxidantes y antimicrobianas del aceite esencial procedente de las partes aérea (hojas y flores) de Chuquiraga arcuataHarling cultivadas en los Andes ecuatorianos. Se identificaron 126 compuestos en el aceite esencial. Los hidrocarburos monoterpénicos (45,8%) y los monoterpenos oxigenados (44,1%) tuvieron el mayor porcentaje. Los compuestos más abundantes fueron alcanfor (21,6%), mirceno (19,5%) y 1,8-cineol (13,4%). La actividadantioxidante se examinó mediante ensayos DPPH, ABTS y FRAP. El aceite esencial tuvo un efecto eliminador moderado y una reducción de la capacidad de iones férricos mediante el ensayo FRAP. Se observó actividad antimicrobiana del aceite esencial contra cuatro bacterias y un hongo patógenos. El aceite esencial mostró actividad contra todas las cepas de microorganismos bajo prueba, particularmente contra Candida albicansy Staphylococcus aureuscon CMI de 2,43-12,10 µg/mL.
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Aceites Volátiles/química , Extractos Vegetales/química , Asteraceae/química , Antiinfecciosos/química , Antioxidantes/química , Bacterias/efectos de los fármacos , Aceites Volátiles/farmacología , Extractos Vegetales/farmacología , Cromatografía de Gases , Hojas de la Planta/química , Monoterpenos/análisis , Ecuador , Hidrocarburos/análisis , Antiinfecciosos/farmacología , Antioxidantes/farmacologíaRESUMEN
Ligularia fischeriTurcz. is a medicinal plant for the treatment of inflammation in China and Korea. Its chemical components in anti-sepsis activity and the related molecular mechanisms remain unknown yet. In this study, two undescribed eremophilane sesquiterpenoids fischerins A (1) and B (2), together with 8 known sesquiterpenoid derivatives (3-10), were isolated from the whole plant of L. fischeri. Their structures were identified by detailed spectroscopic and ECD analyses. 3-Oxo-8-hydroxyeremophila-1,7(11)-dien-12,8-olide (6) showed the most inhibitory effect on NO production in LPS-stimulated RAW 264.7 cells with the IC50 value of 6.528 µM. Meanwhile, compound 6 also decreased the mRNA expression of pro-inflammatory factors IFN-γ, IL-1ß, IL-6 and TNF-α via downregulating NF-κB signaling pathway in vitro. Furthermore, compound 6 reduced the mortality, murine sepsis score, the serum TNF-α level and organic damage in a mouse model of sepsis. These findings indicated that compound 6 possessed the potent anti-inflammatory activity and had the potential as a promising drug candidate for sepsis therapy.
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Antiinflamatorios , Asteraceae , FN-kappa B , Sepsis , Sesquiterpenos , Animales , Ratones , Sesquiterpenos/farmacología , Sesquiterpenos/aislamiento & purificación , Asteraceae/química , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Estructura Molecular , Células RAW 264.7 , Sepsis/tratamiento farmacológico , FN-kappa B/metabolismo , Masculino , Óxido Nítrico/metabolismo , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , China , Citocinas/metabolismoRESUMEN
Natural products are an unsurpassed source of leading structures in drug discovery. The biosynthetic machinery of the producing organism offers an important source for modifying complex natural products, leading to analogs that are unattainable by chemical semisynthesis or total synthesis. In this report, through the combination of natural products chemistry and diversity-oriented synthesis, a diversity-enhanced extracts approach is proposed using chemical reactions that remodel molecular scaffolds directly on extracts of natural resources. This method was applied to subextract enriched in sesquiterpene lactones from Ambrosia tenuifolia (Fam. Asteraceae) using acid media conditions (p-toluenesulfonic acid) to change molecular skeletons. The chemically modified extract was then fractionated by a bioguided approach to obtain the pure compounds responsible for the anti-glioblastoma (GBM) activity in T98G cell cultures. Indeed, with the best candidate, chronobiological experiments were performed to evaluate temporal susceptibility to the treatment on GBM cell cultures to define the best time to apply the therapy. Finally, bioinformatics tools were used to supply qualitative and quantitative information on the physicochemical properties, chemical space, and structural similarity of the compound library obtained. As a result, natural products derivatives containing new molecular skeletons were obtained, with possible applications as chemotherapeutic agents against human GBM T98G cell cultures.
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Glioblastoma , Extractos Vegetales , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patología , Línea Celular Tumoral , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Productos Biológicos/química , Productos Biológicos/farmacología , Asteraceae/química , Sesquiterpenos/química , Sesquiterpenos/farmacología , Lactonas/química , Lactonas/farmacología , Antineoplásicos/farmacología , Antineoplásicos/químicaRESUMEN
BACKGROUND: Spilanthes filicaulis (Schumach. & Thonn.) C. D Adam is a shrubby plant of the Asteraceae family that has medicinal benefits for the pharmaceutical and cosmetic industries. PURPOSE: The purpose of this study was to assess the effectiveness of Spilanthes filicaulis leaf extract in a streptozotocin (STZ)-induced rat model and the associated signaling pathways. METHODS: A sample of 25 male Wistar rats was randomly assigned to groups I, II, III, IV, and V. Each group included five animals, i.e., control rats, diabetic control rats, diabetic rats treated with metformin, and diabetic rats treated with 150 mg/kg/bw and 300 mg/kg/bw of the methanolic extract of S. filicaulis leaves (MESFL). Treatment was administered for 15 successive days via oral gavage. After 15 days, the rats were evaluated for fasting blood glucose (FBG), glycated hemoglobin (HbA1c), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (MDA), hexokinase, and glucose-6-phosphatase activities. Gene expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor gamma (PPAR-γ), kelch-like ECH-associated protein 1 (Keap1), protein tyrosine phosphatase 1B (PTP1B) and the antiapoptotic protein caspase-3 were examined. RESULTS: MESFL was administered to diabetic rats, and changes in body weight, fasting blood glucose (FBG) and HbA1c were restored. Furthermore, in diabetic rats, S. filicaulis significantly reduced the levels of triglycerides (TGs), total cholesterol (TC), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) and significantly increased HDL. S. filicaulis improved ALT, AST, and ALP enzyme activity in diabetic rats. MDA levels decreased considerably with increasing activity of antioxidant enzymes, such as GST, SOD, CAT and GSH, in diabetic liver rats treated with S. filicaulis. Diabetic rats treated with MESFL and metformin exhibited upregulated mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor gamma (PPAR-γ). Kelch-like ECH-associated protein 1 (Keap1) and protein tyrosine phosphatase 1B (PTP1B) mRNA expression in the liver was downregulated in diabetic rats treated with MESFL and metformin. In addition, MESFL downregulated the mRNA expression of caspase-3 in diabetic rats. CONCLUSION: It can be concluded from the data presented in this study that MESFL exerts a protective effect on diabetic rats due to its antidiabetic, antioxidant, antihyperlipidemic and antiapoptotic effects and may be considered a treatment for T2DM.
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Diabetes Mellitus Experimental , Proteína 1 Asociada A ECH Tipo Kelch , Hígado , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , PPAR gamma , Extractos Vegetales , Hojas de la Planta , Proteína Tirosina Fosfatasa no Receptora Tipo 1 , Ratas Wistar , Transducción de Señal , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Masculino , Extractos Vegetales/farmacología , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Estrés Oxidativo/efectos de los fármacos , Hojas de la Planta/química , Transducción de Señal/efectos de los fármacos , Ratas , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , PPAR gamma/metabolismo , PPAR gamma/genética , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo , Asteraceae/química , Estreptozocina , Hipoglucemiantes/farmacologíaRESUMEN
Parthenium hysterophorus L., an invasive alien species and notorious weed, offers various benefits to the medical and agrochemical industries. This study aimed to evaluate the antioxidant and insecticidal activities of P. hysterophorus flower extract and conduct chemical profiling to identify the phytoconstituents responsible for these biological effects. The antioxidant activity was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, while gas chromatography mass spectrometry (GCMS) analysis was employed for chemical configuration evaluation. Our findings demonstrate that the dichloromethane (DCM) extract of P. hysterophorus exhibits potent radical scavenging activity (95.03%). Additionally, phytochemical analysis revealed significant amounts of phenols and flavonoids in the distilled water and ethyl acetate extracts (103.30 GAEg-1 and 138.67 QEg-1, respectively). In terms of insecticidal activity, the flower extract displayed maximum mortality rates of 63.33% and 46.67% after 96 hours of exposure at concentrations of 1000 µgmL-1 and 800 µgmL-1, respectively, with similar trends observed at 72 hours. Furthermore, the P. hysterophorus extracts exhibited LC50 values of 1446 µgmL-1 at 72 hours and 750 µgmL-1 at 96 hours. Imidacloprid, the positive control, demonstrated higher mortality rates at 96 hours (97.67%) and 72 hours (91.82%). Moreover, the antioxidant activity of P. hysterophorus extracts exhibited a strong correlation with phenols, flavonoids, and extract yield. GCMS analysis identified 13 chemical compounds, accounting for 99.99% of the whole extract. Ethanol extraction yielded the highest percentage of extract (4.34%), followed by distilled water (3.22%), ethyl acetate (3.17%), and dichloromethane (2.39%). The flower extract of P. hysterophorus demonstrated significant antioxidant and insecticidal activities, accompanied by the presence of valuable chemical compounds responsible for these biological effects, making it a promising alternative to synthetic agents. These findings provide a novel and fundamental basis for further exploration in purifying the chemical compounds for their biological activities.
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Antioxidantes , Asteraceae , Flores , Insecticidas , Extractos Vegetales , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antioxidantes/farmacología , Antioxidantes/química , Insecticidas/farmacología , Insecticidas/química , Asteraceae/química , Animales , Flores/química , Cromatografía de Gases y Espectrometría de Masas , Flavonoides/análisis , Flavonoides/química , Fenoles/análisis , Fenoles/química , Parthenium hysterophorusRESUMEN
Herein, 17 previously undescribed polyacetylenes and 9 known ones were isolated from Tridax procumbens L. Their structures were identified using spectroscopic techniques (NMR, UV, IR, MS and optical rotation), the modified Mosher method, electronic circular dichroism (ECD) data and ECD calculation. The cytotoxicity of polyacetylenes on six human tumour cell lines (K562, K562/ADR, AGS, MGC-803, SPC-A-1 and MDA-MB-231) was evaluated. (3S,10R)-tridaxin B (2a), (3S,10S)-tridaxin B (2b) and tridaxin F (8) demonstrated substantial cytotoxic effects against the K562 cell line, with half-maximal inhibitory concentration (IC50) values of 2.62, 14.43 and 17.91 µM, respectively. Cell and nucleus morphology assessments and Western blot analysis confirmed that the cytotoxicity of the three polyacetylenes on K562 cells was mediated through a dose-dependent apoptosis pathway. Furthermore, (3S,10R)-tridaxin A (1a) and tridaxin G (9) exhibited considerable inhibitory effects on lipopolysaccharide-stimulated nitric oxide production in RAW 264.7 macrophages, with IC50 values of 15.92 and 20.35 µM, respectively. Further investigations revealed that 9 exerted anti-inflammatory activities by impeding the nuclear translocation of NF-κB and down-regulating the expression of pro-inflammatory factors, including those of iNOS, COX-2, IL-1ß and IL-6, in a concentration-dependent manner. The study provides evidence that polyacetylenes from T. procumbens may serve as a potential source of anti-tumour or anti-inflammatory agents for treating related diseases.
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Antiinflamatorios , Antineoplásicos Fitogénicos , Poliinos , Humanos , Poliinos/farmacología , Poliinos/química , Poliinos/aislamiento & purificación , Ratones , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Apoptosis/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células RAW 264.7 , Estructura Molecular , Relación Dosis-Respuesta a Droga , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Asteraceae/química , Células K562 , Relación Estructura-Actividad , Proliferación Celular/efectos de los fármacos , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , FN-kappa B/metabolismo , FN-kappa B/antagonistas & inhibidores , Línea Celular TumoralRESUMEN
Among the actinomycetes in the rare genera, Micromonospora is of great interest since it has been shown to produce novel therapeutic compounds. Particular emphasis is now on its isolation from plants since its population from soil has been extensively explored. The strain CR3 was isolated as an endophyte from the roots of Hieracium canadense, and it was identified as Micromonospora chokoriensis through 16S gene sequencing and phylogenetic analysis. The in-vitro analysis of its extract revealed it to be active against the clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Candida tropicalis (15 mm). No bioactivity was observed against Gram-negative bacteria, Escherichia coli ATCC 25922, and Klebsiella pneumoniae ATCC 706003. The Micromonospora chokoriensis CR3 extract was also analyzed through the HPLC-DAD-UV-VIS resident database, and it gave a maximum match factor of 997.334 with the specialized metabolite BagremycinA (BagA). The in-silico analysis indicated that BagA strongly interacted with the active site residues of the sterol 14-α demethylase and thymidylate kinase enzymes, with the lowest binding energies of - 9.7 and - 8.3 kcal/mol, respectively. Furthermore, the normal mode analysis indicated that the interaction between these proteins and BagA was stable. The DFT quantum chemical properties depicted BagA to be reasonably reactive with a HOMO-LUMO gap of (ΔE) of 4.390 eV. BagA also passed the drug-likeness test with a synthetic accessibility score of 2.06, whereas Protox-II classified it as a class V toxicity compound with high LD50 of 2644 mg/kg. The current study reports an endophytic actinomycete, M. chokoriensis, associated with H. canadense producing the bioactive metabolite BagA with promising antimicrobial activity, which can be further modified and developed into a safe antimicrobial drug.
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Micromonospora , Micromonospora/metabolismo , Micromonospora/genética , Asteraceae/microbiología , Asteraceae/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Filogenia , Antibacterianos/farmacología , Antibacterianos/biosíntesis , Antibacterianos/química , Simulación por Computador , Simulación del Acoplamiento Molecular , Candida tropicalis/efectos de los fármacos , Candida tropicalis/metabolismo , Teoría Funcional de la Densidad , Antiinfecciosos/farmacología , Antiinfecciosos/química , Raíces de Plantas/microbiologíaRESUMEN
Malathion (MAL) is one of the highly toxic organophosphorus (OP) compounds that induces hepatotoxicity. Echinops. ritro leaves extract (ERLE) is traditionally used in the treatment of bacterial/fungal infections. This study's goal was to investigate the potential of extracts from ERLE against hepatotoxicity induced by MAL in male albino rats. Four equal groups of forty mature male albino rats were created: The rats in the first group used as a control. The second group of rats received ERLE orally. The third group received MAL. ERLE and MAL were administered to the fourth group of rats. Six-week treatment groups were conducted. Using lipid peroxidation indicators [malondialdehyde (MDA), alanine aminotransferase (ALT), aspartate aminotransferase (AST)], oxidative stress markers [catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)], apoptotic markers [Bcl-2 & caspase-3] and tumor necrosis factor alpha (TNF-α). Rats treated with MAL underwent a significant increase on MDA, ALT, AST, caspase-3 and TNF-α marker with a significant decrease in antioxidant markers [CAT, SOD, GPx] and Bcl-2. Histologically, MAL-treated group's liver sections displayed damaged hepatocytes with collapsed portions, pyknotic nuclei, vacuolated cytoplasm, and congested central veins. Ultra structurally, rat livers treated with MAL showed dilated cisternae of endoplasmic reticulum, swollen mitochondria with disrupted cristae, nuclei with disrupted chromatin content, multiple lysosomes, multiple vacuolations and a disrupted blood sinusoid. With rats treated with ERLE, these alterations were essentially non-existent. It is possible to conclude that ERLE protects against MAL hepatotoxicity, and that this protection is related, at least in part, to its antioxidant activities.
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Apoptosis , Enfermedad Hepática Inducida por Sustancias y Drogas , Malatión , Estrés Oxidativo , Extractos Vegetales , Animales , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Apoptosis/efectos de los fármacos , Masculino , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Ratas , Malatión/toxicidad , Inflamación/tratamiento farmacológico , Hígado/efectos de los fármacos , Hígado/patología , Antioxidantes/farmacología , Alanina Transaminasa/sangre , Peroxidación de Lípido/efectos de los fármacos , Aspartato Aminotransferasas/sangre , Asteraceae/químicaRESUMEN
Polyphenols are ubiquitous plant metabolites that demonstrate biological activities essential to plant-environment interactions. They are of interest to plant food consumers, as well as to the food, pharmaceutical and cosmetic industry. The class of the plant metabolites comprises both widespread (chlorogenic acids, luteolin, quercetin) and unique compounds of diverse chemical structures but of the common biosynthetic origin. Polyphenols next to sesquiterpenoids are regarded as the major class of the Inuleae-Inulinae metabolites responsible for the pharmacological activity of medicinal plants from the subtribe (Blumea spp., Dittrichia spp., Inula spp., Pulicaria spp. and others). Recent decades have brought a rapid development of molecular and analytical techniques which resulted in better understanding of the taxonomic relationships within the Inuleae tribe and in a plethora of data concerning the chemical constituents of the Inuleae-Inulinae. The current taxonomical classification has introduced changes in the well-established botanical names and rearranged the genera based on molecular plant genetic studies. The newly created chemical data together with the earlier phytochemical studies may provide some complementary information on biochemical relationships within the subtribe. Moreover, they may at least partly explain pharmacological activities of the plant preparations traditionally used in therapy. The current review aimed to systematize the knowledge on the polyphenols of the Inulae-Inulinae.
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Polifenoles , Polifenoles/química , Polifenoles/farmacología , Humanos , Plantas Medicinales/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Fitoquímicos/química , Fitoquímicos/farmacología , Asteraceae/químicaRESUMEN
Blumea eriantha D.C is a weed from Asteraceae family and is reported to have anticancer activity. The essential oil from the aerial parts was extracted by steam distillation method with the yield of 0.36%. Through GC-MS analysis of the oil, seventeen compounds could be identified by comparing with linear retention indices with the library. Out of the seventeen compounds ß-Caryophylline oxide was isolated by column chromatography with gradient elution and the structure was determined through FT-IR, MS, 1HNMR, 13 C NMR and DEPT. The oil was evaluated for its effect on angiogenesis using Chorioallantoic Membrane Assay (CAM Assay). The concentration dependent antiangiogenic effect was observed with IC 50 value of 19.28 ppm.